Tying-Up / Exertional Rhabdomyolysis

Tying-up, clinically known as exertional rhabdomyolysis, is a syndrome of muscle damage that occurs in horses during or shortly after exercise. This condition involves the breakdown of skeletal muscle cells, releasing their contents including myoglobin and muscle enzymes into the bloodstream. The term tying-up describes the characteristic appearance of affected horses, which become stiff and reluctant to move as if their muscles have locked up or tied into knots. Severe episodes constitute true medical emergencies requiring immediate veterinary intervention to prevent potentially fatal complications including kidney failure.

The prevalence of tying-up varies significantly among horse populations, with certain breeds and disciplines showing markedly higher incidence. Studies suggest that between 5 and 10 percent of Thoroughbred racehorses experience at least one episode during their careers, while some breeding lines show much higher susceptibility. Quarter Horses involved in activities requiring bursts of intense work face elevated risk, as do Arabians and Warmblood sport horses. The condition affects horses of all ages but commonly first appears in young horses entering training, with females often more frequently affected than males in some forms of the disease.

The impact of tying-up on equine health and performance ranges from mild, self-limiting episodes to career-ending or life-threatening events. Mild cases may cause temporary stiffness and discomfort that resolves within hours, while severe episodes result in profound muscle necrosis, dark brown urine from myoglobin release, and potential acute kidney injury. Recurrent tying-up significantly affects training schedules and competitive careers, as affected horses require careful management to prevent repeated episodes. The economic impact includes veterinary costs, lost training days, and reduced competitive potential.

Understanding that tying-up represents a syndrome with multiple underlying causes rather than a single disease has revolutionized equine medicine's approach to this condition. Research has identified several distinct forms including polysaccharide storage myopathy (PSSM), recurrent exertional rhabdomyolysis (RER), and sporadic cases related to overexertion or metabolic imbalances. Accurate diagnosis of the specific form affecting an individual horse enables targeted treatment and management strategies that dramatically improve outcomes. Early recognition of symptoms and immediate appropriate response are essential for minimizing muscle damage and preventing complications.

The primary causes of tying-up encompass several distinct pathophysiological mechanisms that produce similar clinical presentations. Polysaccharide storage myopathy (PSSM) results from abnormal glycogen accumulation in muscle cells due to genetic mutations affecting carbohydrate metabolism. Type 1 PSSM, caused by a mutation in the GYS1 gene, leads to excessive glycogen synthesis and storage that damages muscle fibers during exercise. Recurrent exertional rhabdomyolysis (RER) involves abnormal calcium regulation within muscle cells, causing sustained contractions and cellular damage. Sporadic tying-up occurs in otherwise normal horses pushed beyond their conditioning level or subjected to metabolic stress.

Genetic and breed predispositions play crucial roles in determining susceptibility to various forms of tying-up. Type 1 PSSM is highly prevalent in Quarter Horses, with studies indicating up to 10 percent of the breed carries the mutation, and even higher percentages in certain bloodlines. Draft breeds including Belgians, Percherons, and their crosses show elevated PSSM prevalence. RER predominantly affects Thoroughbreds, Standardbreds, and Arabians, with clear familial patterns suggesting strong hereditary components. A specific genetic mutation for RER has not been definitively identified, but research indicates complex inheritance patterns involving multiple genes.

Environmental and management factors significantly influence the likelihood of tying-up episodes even in genetically predisposed horses. Inconsistent exercise schedules, particularly extended rest periods followed by sudden intense work, dramatically increase risk. Diets high in starch and sugar exacerbate PSSM by providing excess substrate for abnormal glycogen synthesis. Inadequate warm-up before strenuous exercise fails to prepare muscles for workload demands. Electrolyte imbalances from sweating, inadequate supplementation, or dietary deficiencies impair normal muscle function. Stress from transport, competition, or environmental changes triggers episodes in susceptible individuals.

Risk factors for tying-up extend beyond genetics to include age, sex, fitness level, and temperament. Young horses in early training commonly experience their first episodes as demands increase beyond previous conditioning. Female horses appear more susceptible to RER than males, possibly related to hormonal influences on muscle cell calcium handling. Horses in heavy training may experience subclinical muscle damage that accumulates and eventually manifests clinically. Nervous, high-strung temperaments correlate with increased RER incidence, suggesting stress hormone involvement. Illness, fever, or other concurrent health issues increase vulnerability to exercise-induced muscle damage.

The pathophysiology of muscle damage in tying-up involves disruption of normal cellular energy metabolism and calcium homeostasis. In PSSM, abnormal glycogen deposits mechanically disrupt muscle fiber structure and impair energy production during exercise. In RER, defective calcium release and reuptake by the sarcoplasmic reticulum cause sustained muscle contraction that depletes energy stores and damages cell membranes. Regardless of the initiating mechanism, the final common pathway involves loss of cell membrane integrity, release of intracellular contents including myoglobin and creatine kinase, and inflammatory responses that extend tissue damage. Myoglobin released into circulation is filtered by the kidneys, where it can precipitate in renal tubules and cause acute kidney injury in severe cases.

Early warning signs of tying-up may be subtle and easily attributed to other causes, making vigilant observation essential for prompt recognition. Affected horses may show mild reluctance to move forward or shortened stride length at the start of exercise. A slight change in movement quality, appearing stiff or choppy rather than fluid, may be noticeable to experienced handlers. Some horses demonstrate vague signs of discomfort such as shifting weight, looking at their flanks, or exhibiting a worried expression. Sweating disproportionate to work intensity or environmental conditions often precedes more obvious symptoms. Horses with chronic or recurrent forms may show subtle performance decline or resistance to work before acute episodes occur.

Common symptoms of established tying-up episodes present a characteristic clinical picture. Affected horses display marked stiffness, particularly in the hindquarters and back muscles, giving a rigid, awkward appearance to their movement. Muscle hardness can be palpated over the gluteal and lumbar regions, feeling firm and boardlike compared to normal tissue. The horse adopts a base-wide stance and shows extreme reluctance to move, sometimes planting all four feet and refusing to take another step. Profuse sweating occurs even without significant exertion, covering the body in lather. Elevated heart and respiratory rates reflect pain and metabolic stress.

Behavioral changes during tying-up episodes reflect the significant pain horses experience. Affected horses appear anxious and distressed, with wide eyes and flared nostrils. They may attempt to lie down but struggle to do so or show discomfort in recumbent positions. Some horses paw the ground, stretch as if attempting to urinate, or repeatedly shift their weight. Complete refusal to move forward, even when urged, is characteristic and should not be interpreted as stubbornness. Horses may vocalize or show signs of colic-like distress, though the muscle involvement is the primary source of discomfort. Depression and reluctance to interact normally may persist after acute symptoms subside.

Physical signs of tying-up extend beyond muscle stiffness to include several measurable abnormalities. Dark reddish-brown to coffee-colored urine indicates myoglobin release from damaged muscle cells, a finding that signals significant tissue destruction and kidney risk. Elevated body temperature occurs from metabolic heat generation and muscle inflammation. Dehydration develops rapidly due to sweating and fluid shifts into damaged tissues. Rapid, shallow breathing reflects pain, metabolic acidosis, and sometimes compromised respiratory muscle function. The muscles of the hindquarters and back may become visibly swollen in severe cases, and careful palpation reveals heat and pain response.

Symptom progression in untreated or severe tying-up follows a predictable pattern of worsening. What begins as mild stiffness can progress to complete inability to move within minutes to hours. Urine color darkens as more myoglobin is released, indicating ongoing muscle destruction. Cardiovascular parameters worsen as dehydration and pain intensify. Some horses become recumbent and unable to rise, a grave prognostic sign. Kidney function may deteriorate as myoglobin accumulates in renal tubules. Without intervention, severely affected horses face risk of kidney failure, cardiac arrhythmias from electrolyte disturbances, and death.

Emergency symptoms requiring immediate veterinary intervention include complete inability or refusal to move, recumbency, dark brown or red urine, severe distress, and any tying-up episode in a horse with history of severe attacks. Horses that show no improvement with rest and initial first aid measures need professional evaluation urgently. Signs of kidney involvement including decreased urine output or cessation of urination constitute emergencies. Any horse that continues to deteriorate despite rest and supportive care requires immediate intensive treatment. Owners should never force a tied-up horse to walk, as continued exercise dramatically worsens muscle damage.

Physical examination of a horse with suspected tying-up reveals characteristic findings that often allow clinical diagnosis. The veterinarian assesses gait quality, muscle palpation findings, heart rate, respiratory rate, and overall demeanor. Hard, painful muscles over the hindquarters and back confirm the diagnosis in most cases. Rectal examination may reveal firm, painful lumbar muscles. Assessment of hydration status through skin turgor and mucous membrane examination guides fluid therapy decisions. Urine color evaluation, when available, provides immediate indication of myoglobin release severity. History taking focuses on recent exercise, diet, previous episodes, and any changes in management.

Diagnostic testing in tying-up cases serves to confirm the diagnosis, assess severity, and identify the underlying form of the condition. Blood samples reveal dramatically elevated muscle enzymes including creatine kinase (CK) and aspartate aminotransferase (AST), with levels correlating to the extent of muscle damage. CK elevations may reach tens of thousands of units per liter in severe cases, compared to normal values under several hundred. Serum chemistry panels assess kidney function through blood urea nitrogen and creatinine measurements. Urinalysis confirms myoglobinuria and helps evaluate kidney status. Complete blood count may show stress-related changes including elevated white blood cell counts.

Advanced diagnostics help differentiate between forms of tying-up and guide long-term management. Muscle biopsy, typically from the semimembranosus or gluteal muscles, allows histopathological examination for abnormal glycogen deposits characteristic of PSSM. Genetic testing for the GYS1 mutation definitively diagnoses Type 1 PSSM through simple hair root or blood samples. Type 2 PSSM, suspected when clinical signs suggest PSSM but genetic testing is negative, requires muscle biopsy for diagnosis. Nuclear scintigraphy can map the extent and location of muscle damage. Ultrasound examination may reveal muscle fiber disruption in severely affected areas. These advanced tests are particularly valuable for horses with recurrent episodes to optimize prevention strategies.

Differential diagnosis for tying-up includes several conditions that may present with similar stiffness or reluctance to move. Colic should be considered given the pain behaviors some horses display, though the muscle involvement and lack of gastrointestinal sounds distinguish tying-up. Laminitis causes reluctance to move but affects the feet rather than hindquarter muscles. Spinal cord disease or injury produces weakness and incoordination rather than the characteristic muscle hardness. Tetanus causes generalized rigidity but includes facial involvement and hypersensitivity to stimuli. Botulism produces weakness and recumbency but with flaccid rather than rigid muscles. Fractures or severe musculoskeletal injuries may cause acute non-weight-bearing lameness requiring differentiation. Accurate diagnosis ensures appropriate treatment and prevents missing serious concurrent conditions.

Emergency and immediate treatment of tying-up focuses on stopping exercise, relieving pain, and preventing further muscle damage. The cardinal rule when tying-up is recognized is to stop exercise immediately and not force the horse to move further, as continued work dramatically worsens muscle destruction. If possible, transport the horse to a stable rather than walking, using a trailer or allowing rest in place until veterinary assistance arrives. Application of warm blankets over the hindquarters helps relax cramping muscles and provides comfort. Pain management through non-steroidal anti-inflammatory drugs such as flunixin meglumine or phenylbutazone should be initiated promptly once veterinary guidance is obtained.

Medical management of tying-up episodes centers on aggressive fluid therapy and supportive care. Intravenous fluid administration corrects dehydration, maintains blood volume, and dilutes myoglobin in the bloodstream to protect kidney function. Large volumes of balanced electrolyte solutions, often 10 to 20 liters or more initially, are typically required for moderate to severe cases. Muscle relaxants such as methocarbamol may be administered to relieve sustained muscle contraction. Sedatives including acepromazine provide pain relief, promote relaxation, and reduce stress. Electrolyte supplementation addresses imbalances from sweating and cellular damage. Severely affected horses may require hospitalization for continued intensive fluid therapy and monitoring.

Surgical intervention is rarely indicated for tying-up itself, though supportive procedures may be necessary in severe cases. Jugular catheter placement facilitates delivery of large fluid volumes and repeated blood sampling. Urinary catheterization allows accurate monitoring of urine output, critical for assessing kidney function in horses with significant myoglobinuria. In extremely rare cases of compartment syndrome from massive muscle swelling, fasciotomy might be considered though this is exceptional. The primary management approach remains medical rather than surgical.

Supportive care during recovery from a tying-up episode requires careful attention to comfort and monitoring. Affected horses benefit from deep bedding to cushion muscles and encourage lying down to rest. Small, frequent feedings of easily digestible forage and senior feeds replace high-starch concentrates. Hand walking should begin only when muscle enzyme levels are declining and the horse moves comfortably, typically starting with 5 to 10 minute sessions. Monitoring continues until muscle enzyme levels return to normal, which may take days to weeks depending on episode severity. Recumbent horses require intensive nursing care including frequent repositioning, padding, and nutritional support.

Rehabilitation and return to work following tying-up must proceed cautiously to prevent recurrence. Rest periods of at least several days allow muscle healing before any exercise resumes. When exercise restarts, beginning with hand walking and gradually increasing duration over days to weeks prevents overwhelming healing tissues. Turnout in small paddocks precedes return to larger spaces where horses might self-exercise excessively. Ridden work resumes at walk only, progressively adding trot and canter over weeks as the horse tolerates increased demands. Monitoring for early warning signs during rehabilitation allows immediate intervention if symptoms recur. Complete recovery may require weeks to months depending on severity.

Treatment decision factors in tying-up cases include episode severity, underlying cause, previous history, and intended use of the horse. Horses with their first mild episode may respond well to basic supportive care and management changes. Recurrent episodes despite management warrant advanced diagnostic workup to identify specific forms requiring targeted interventions. The presence of dark urine or elevated kidney parameters signals need for aggressive treatment and guarded short-term prognosis. Horses intended for athletic careers require thorough investigation and optimized prevention strategies. Economic considerations including prolonged recovery time and management changes should be discussed realistically with owners. Horses with severe recurrent disease unresponsive to management may face limited career options.

Recovery timeline for tying-up varies considerably based on episode severity and underlying cause. Mild episodes with modest enzyme elevations may resolve within two to three days of rest and supportive care, with horses returning to light work within a week or two. Moderate episodes typically require one to two weeks of rest followed by gradual return to exercise over additional weeks. Severe episodes with marked myoglobinuria and muscle necrosis may necessitate months of recovery, and some horses experience permanent muscle damage affecting future soundness. Monitoring muscle enzyme levels guides decisions about when activity can safely increase, with CK and AST values returning to normal before work resumes.

Post-treatment care and monitoring requirements extend well beyond the acute episode. Dietary modifications appropriate to the specific form of tying-up should be implemented immediately and maintained long-term. For PSSM horses, transitioning to low-starch, high-fat diets requires gradual introduction over several weeks to allow metabolic adaptation. Exercise programs must be restructured to provide consistent daily work rather than sporadic intense sessions. Regular follow-up blood work confirms muscle enzyme levels remain normal as activity increases. Monitoring for subtle signs of impending episodes during work allows early intervention before significant damage occurs.

Prognosis factors for tying-up outcomes include the specific form of disease, episode severity, compliance with management recommendations, and individual horse variation. Horses with sporadic exertional rhabdomyolysis related to overexertion often have excellent prognoses with appropriate conditioning. PSSM horses managed with proper diet and exercise can often perform successfully though remain predisposed to episodes if management lapses. RER horses tend to have more variable prognoses, with some achieving long competitive careers while others experience frustrating recurrent episodes despite optimal management. Horses that experience severe myoglobinuria with kidney compromise have guarded immediate prognoses and potentially compromised long-term function.

Long-term soundness outlook for tying-up survivors depends heavily on achieving effective management strategies. Many horses with identified forms of exertional rhabdomyolysis perform at high levels when diet and exercise are optimized. Some competitive Thoroughbreds with managed RER have successful racing careers. PSSM horses often thrive in lower-intensity disciplines with consistent management. Horses that experience repeated severe episodes despite intervention may face career limitations or retirement. The psychological impact of painful episodes may affect some horses' willingness to work, requiring patient retraining. Owners should understand that management is typically lifelong, as underlying predispositions remain even when clinical episodes are prevented.

Management practices form the cornerstone of tying-up prevention for susceptible horses. Consistent daily exercise, even if brief, prevents the muscle glycogen accumulation that triggers episodes in rest-followed-by-work scenarios. The traditional Monday morning disease pattern reflects horses receiving full grain rations over weekend rest then working intensely Monday, a scenario prevented by exercising seven days weekly. Warm-up periods before strenuous work prepare muscles metabolically and improve blood flow. Cool-down periods allow gradual metabolic transition and waste product clearance. Maintaining consistent routines reduces stress-related triggers. Transportation should include rest stops and attention to hydration.

Nutritional prevention strategies differ based on the specific form of tying-up affecting an individual horse. For PSSM horses, dramatic reduction in dietary starch and sugar is essential, typically targeting less than 10 to 12 percent of daily calories from non-structural carbohydrates. Fat supplementation replaces starch as an energy source, often providing 15 to 25 percent of daily calories from fat. Appropriate forage-based diets with limited or no grain help control glycemic response. For RER horses, maintaining appropriate calcium and electrolyte balance supports normal muscle function. Adequate selenium and vitamin E intake ensures antioxidant protection against muscle damage. Feeding schedules should avoid large meals before exercise.

Exercise and conditioning practices tailored to tying-up prevention require careful planning and consistency. Daily turnout or exercise, even 20 to 30 minutes of walking, dramatically reduces episode frequency. Gradual increases in work intensity allow muscles to adapt without overwhelming cellular metabolism. Avoiding sudden increases in workload, particularly after rest periods, prevents sporadic episodes in any horse. Training schedules should accommodate individual horse responses, with increased recovery time for those showing early warning signs. Competition schedules must consider travel stress and modified routines as risk factors requiring compensatory management.

Environmental factors influencing tying-up risk require attention in overall prevention planning. Temperature extremes stress metabolic regulation and may trigger episodes in susceptible horses. Hot, humid conditions increase sweating and electrolyte losses requiring supplementation. Cold weather may encourage inadequate warm-up before work. Stall rest during inclement weather should be accompanied by reduced or modified concentrate feeding. Travel to competitions creates multiple risk factors including stress, routine disruption, and variable exercise, requiring careful management. Facility design allowing daily turnout reduces forced rest periods.

Supplementation protocols for tying-up prevention address specific metabolic needs. Vitamin E supplementation at 2000 to 5000 IU daily provides antioxidant protection for muscle cell membranes. Selenium supplementation should be guided by regional soil levels and forage analysis to achieve adequate but not excessive intake. Electrolyte supplementation replaces losses from sweating during exercise and warm weather. Some practitioners recommend chromium supplementation to improve insulin sensitivity in PSSM horses. Various muscle support supplements are marketed though evidence for efficacy varies. Supplementation should be coordinated with veterinary guidance to avoid imbalances or toxicity.

Daily management adjustments for horses with tying-up predisposition require commitment to consistent routines. Every day should include some form of exercise or turnout, eliminating rest days that allow glycogen accumulation in PSSM horses or create sporadic work patterns triggering RER. Morning feeding should be timed appropriately before exercise, typically allowing digestion before work begins. Monitoring begins before tacking up, assessing attitude, movement, and any subtle stiffness suggesting an impending episode. Keeping detailed records of exercise, diet, and any symptoms helps identify patterns and optimize management. Communication between all handlers ensures consistent approach regardless of who works with the horse.

Housing and turnout considerations significantly impact tying-up management success. Daily turnout provides natural exercise even when formal work sessions are not possible. Paddock size and footing should encourage movement rather than standing. Group turnout may increase activity through social interaction if compatible horses are available. Stall rest should be minimized to only when absolutely necessary, with feed adjusted accordingly. Housing location away from stress-inducing neighbors or activities helps reduce RER triggers in nervous horses. Facilities allowing year-round turnout regardless of weather provide significant management advantages.

Exercise modifications for tying-up prone horses follow specific guidelines to minimize episode risk. Extended warm-up periods of 15 to 20 minutes at walk prepare muscles before trot or canter work. Gradual intensity increases throughout training sessions prevent sudden metabolic demands. Recognition of early warning signs such as reluctance or subtle stiffness allows immediate workload reduction before clinical episodes develop. Cool-down periods of similar duration to warm-up allow gradual metabolic transition. Rest days should be replaced with light work or turnout rather than complete inactivity. Competition schedules may need modification to accommodate warm-up needs and avoid back-to-back intense efforts.

Monitoring and ongoing care requirements for tying-up management include regular veterinary involvement. Periodic blood work confirms muscle enzyme levels remain normal, with increased frequency during training intensification. Body condition monitoring ensures appropriate weight, as obesity worsens PSSM symptoms while excessive thinness compromises overall health. Regular assessment of diet adequacy adjusts for changing work levels, growth, or seasonal variations. Farrier care maintains proper hoof balance supporting correct movement. Dental care ensures efficient feed utilization. Any concurrent health issues should be managed promptly as illness increases tying-up vulnerability.

Quality of life and use considerations for horses with exertional rhabdomyolysis require realistic assessment of capabilities and limitations. Many affected horses lead full athletic lives with proper management, competing successfully across disciplines. Some horses require modification of their original intended use based on recurrence patterns despite optimal care. Owner commitment to management protocols determines outcomes more than the diagnosis itself in many cases. Retirement decisions should consider whether appropriate management can be maintained, as horses with well-controlled tying-up often have excellent quality of life continuing in work. Breeding considerations should include the hereditary nature of many forms, particularly PSSM, when planning matings.

High-risk breeds for tying-up vary based on the specific form of exertional rhabdomyolysis. Quarter Horses show the highest prevalence of Type 1 PSSM, with genetic testing studies revealing carrier rates of 10 percent or higher in the general population and substantially higher in halter horse bloodlines. Related breeds including Paint Horses, Appaloosas, and Quarter Horse crosses share this elevated risk. Draft breeds including Belgians, Percherons, and Clydesdales demonstrate high PSSM prevalence, often Type 2 PSSM which requires muscle biopsy for diagnosis. Warmblood breeds show variable PSSM prevalence that appears to be increasing. Thoroughbreds and Standardbreds most commonly experience RER rather than PSSM, with certain bloodlines showing marked susceptibility. Arabians and Arabian crosses may experience either form depending on ancestry.

Use and discipline considerations create additional risk stratification beyond breed. Racing Thoroughbreds and Standardbreds face high demands and intense intermittent work that triggers RER. Quarter Horses used for reining, cutting, and barrel racing perform explosive work that stresses muscle metabolism. Eventing and jumping horses experience intense efforts during competition that may trigger episodes in predisposed individuals. Endurance horses face prolonged metabolic stress requiring careful electrolyte management. Draft horses used for pulling and driving experience sustained intense muscle work. Show horses on inconsistent schedules risk sporadic episodes from weekend-only work patterns. Any discipline involving irregular exercise schedules increases risk regardless of breed.

Genetic testing and breeding recommendations have become increasingly important for tying-up management. Testing for the Type 1 PSSM GYS1 mutation is readily available and recommended for all Quarter Horses, Paints, Appaloosas, and Draft breed horses intended for breeding. Breeding two carriers produces 25 percent affected offspring, making informed mating decisions essential. Some breed registries have implemented or considered testing requirements. RER lacks a definitive genetic test currently, making pedigree analysis and performance history important breeding considerations. Prospective buyers should request genetic testing results and performance history regarding tying-up episodes. Disclosure of known affected status in sales is ethically important and increasingly expected.

Commonly co-occurring conditions with tying-up reflect shared metabolic disturbances and management challenges. Polysaccharide storage myopathy horses frequently demonstrate insulin dysregulation resembling equine metabolic syndrome. Obesity commonly accompanies PSSM and worsens clinical signs while complicating dietary management. Gastric ulcers may develop from NSAID use for episode treatment or from stress in nervous horses prone to RER. Electrolyte imbalances including hypochloremia and hypokalemia may persist in horses with recurrent episodes. Kidney disease may complicate severe cases with myoglobinuria. Shivers and fibrotic myopathy share some features with PSSM and may co-occur.

Conditions with similar symptoms to tying-up require differentiation for appropriate management. Colic produces pain behaviors and reluctance to move but lacks the characteristic muscle involvement and enzyme elevations. Laminitis causes severe lameness and reluctance to walk but affects the feet with characteristic stance. Tetanus produces muscle rigidity but with distinctive facial involvement, third eyelid prolapse, and hypersensitivity. Back pain from various causes may produce stiffness and shortened stride but without the acute episode pattern or laboratory changes. Neurological conditions including EPM and wobbler syndrome cause gait abnormalities but typically with weakness rather than painful muscle cramping. Exhausted horse syndrome after prolonged exertion may resemble severe tying-up.

Potential complications of tying-up extend to several organ systems beyond the muscles. Acute kidney injury from myoglobin precipitation in renal tubules represents the most serious immediate complication of severe episodes. Cardiac arrhythmias may develop from electrolyte disturbances, particularly potassium shifts from damaged cells. Respiratory compromise can occur if respiratory muscles are severely affected. Permanent muscle fibrosis and wasting may follow severe episodes, affecting future soundness. Psychological effects including exercise aversion may develop in horses experiencing repeated painful episodes. Secondary injuries from falling or struggling during severe episodes include fractures and soft tissue trauma. Disseminated intravascular coagulation has been reported in extreme cases with massive muscle necrosis.